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Impact of timing and combination of different BNT162b2 and ChAdOx1-S COVID-19 basic and booster vaccinations on humoral immunogenicity and reactogenicity in adults.

ABSTRACT: In this single-center observational study with 1,206 participants, we prospectively evaluated SARS-CoV-2-antibodies (anti-S RBD) and vaccine-related adverse drug reactions (ADR) after basic and booster immunization with BNT162b2- and ChAdOx1-S-vaccines in four vaccination protocols: Homologous BNT162b2-schedule with second vaccination at either three or six weeks, homologous ChAdOx1-S-vaccination or heterologous ChAdOx1-S/BNT162b2-schedule, each at 12 weeks. All participants received a BNT162b2 booster. Blood samples for anti-S RBD analysis were obtained multiple times over a period of four weeks to six months after basic vaccination, immediately before, and up to three months after booster vaccination. After basic vaccination, the homologous ChAdOx1-S-group showed the lowest anti-S RBD levels over six months, while the heterologous BNT162b2-ChAdOx1-S-group demonstrated the highest anti-S levels, but failed to reach level of significance compared with the homologous BNT162b2-groups. Antibody levels were higher after an extended vaccination interval with BNT162b2. A BNT162b2 booster increased anti-S-levels 11- to 91-fold in all groups, with the homologous ChAdOx1-S-cohort demonstrated the highest increase in antibody levels. No severe or serious ADR were observed. The findings suggest that a heterologous vaccination schedule or prolonged vaccination interval induces robust humoral immunogenicity with good tolerability. Extending the time to boost-immunization is key to both improving antibody induction and reducing ADR rate.

SUBMITTER: Dedroogh S

PROVIDER: S-EPMC10239043 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Impact of timing and combination of different BNT162b2 and ChAdOx1-S COVID-19 basic and booster vaccinations on humoral immunogenicity and reactogenicity in adults.

Dedroogh Simon S Schmiedl Sven S Thürmann Petra A PA Graf Katharina K Appelbaum Sebastian S Koß Reinhard R Theis Christian C Zia Zewarudin Z Tebbenjohanns Jürgen J Thal Serge C SC Dedroogh Michael M

Scientific reports 20230603 1

In this single-center observational study with 1,206 participants, we prospectively evaluated SARS-CoV-2-antibodies (anti-S RBD) and vaccine-related adverse drug reactions (ADR) after basic and booster immunization with BNT162b2- and ChAdOx1-S-vaccines in four vaccination protocols: Homologous BNT162b2-schedule with second vaccination at either three or six weeks, homologous ChAdOx1-S-vaccination or heterologous ChAdOx1-S/BNT162b2-schedule, each at 12 weeks. All participants received a BNT162b2 ...[more]

PMID: 37270632

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Project description:BackgroundTo date, no immunological data on COVID-19 heterologous vaccination schedules in humans have been reported. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech, Mainz, Germany) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, AstraZeneca, Oxford, UK).MethodsWe did a phase 2, open-label, randomised, controlled trial on adults aged 18-60 years, vaccinated with a single dose of ChAdOx1-S 8-12 weeks before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either BNT162b2 (0·3 mL) via a single intramuscular injection (intervention group) or continue observation (control group). The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibody functionality was assessed using a pseudovirus neutralisation assay, and cellular immune response using an interferon-γ immunoassay. The safety outcome was 7-day reactogenicity, measured as solicited local and systemic adverse events. The primary analysis included all participants who received at least one dose of BNT162b2 and who had at least one efficacy evaluation after baseline. The safety analysis included all participants who received BNT162b2. This study is registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739), and is ongoing.FindingsBetween April 24 and 30, 2021, 676 individuals were enrolled and randomly assigned to either the intervention group (n=450) or control group (n=226) at five university hospitals in Spain (mean age 44 years [SD 9]; 382 [57%] women and 294 [43%] men). 663 (98%) participants (n=441 intervention, n=222 control) completed the study up to day 14. In the intervention group, geometric mean titres of RBD antibodies increased from 71·46 BAU/mL (95% CI 59·84-85·33) at baseline to 7756·68 BAU/mL (7371·53-8161·96) at day 14 (p<0·0001). IgG against trimeric spike protein increased from 98·40 BAU/mL (95% CI 85·69-112·99) to 3684·87 BAU/mL (3429·87-3958·83). The interventional:control ratio was 77·69 (95% CI 59·57-101·32) for RBD protein and 36·41 (29·31-45·23) for trimeric spike protein IgG. Reactions were mild (n=1210 [68%]) or moderate (n=530 [30%]), with injection site pain (n=395 [88%]), induration (n=159 [35%]), headache (n=199 [44%]), and myalgia (n=194 [43%]) the most commonly reported adverse events. No serious adverse events were reported.InterpretationBNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response, with an acceptable and manageable reactogenicity profile.FundingInstituto de Salud Carlos III.TranslationsFor the French and Spanish translations of the abstract see Supplementary Materials section.

Project description:BackgroundHeterologous vaccine regimens have been widely discussed as a way to mitigate intermittent supply shortages and to improve immunogenicity and safety of COVID-19 vaccines. We aimed to assess the reactogenicity and immunogenicity of heterologous immunisations with ChAdOx1 nCov-19 (AstraZeneca, Cambridge, UK) and BNT162b2 (Pfizer-BioNtech, Mainz, Germany) compared with homologous BNT162b2 and ChAdOx1 nCov-19 immunisation.MethodsThis is an interim analysis of a prospective observational cohort study enrolling health-care workers in Berlin (Germany) who received either homologous ChAdOx1 nCov-19 or heterologous ChAdOx1 nCov-19-BNT162b2 vaccination with a 10-12-week vaccine interval or homologous BNT162b2 vaccination with a 3-week vaccine interval. We assessed reactogenicity after the first and second vaccination by use of electronic questionnaires on days 1, 3, 5, and 7. Immunogenicity was measured by the presence of SARS-CoV-2-specific antibodies (full spike-IgG, S1-IgG, and RBD-IgG), by an RBD-ACE2 binding inhibition assay (surrogate SARS-CoV-2 virus neutralisation test), a pseudovirus neutralisation assay against two variants of concerns (alpha [B.1.1.7] and beta [B.1.351]), and anti-S1-IgG avidity. T-cell reactivity was measured by IFN-γ release assay.FindingsBetween Dec 27, 2020, and June 14, 2021, 380 participants were enrolled in the study, with 174 receiving homologous BNT162b2 vaccination, 38 receiving homologous ChAdOx1 nCov-19 vaccination, and 104 receiving ChAdOx1 nCov-19-BNT162b2 vaccination. Systemic symptoms were reported by 103 (65%, 95% CI 57·1-71·8) of 159 recipients of homologous BNT162b2, 14 (39%, 24·8-55·1) of 36 recipients of homologous ChAdOx1 nCov-19, and 51 (49%, 39·6-58·5) of 104 recipients of ChAdOx1 nCov-19-BNT162b2 after the booster immunisation. Median anti-RBD IgG levels 3 weeks after boost immunisation were 5·4 signal to cutoff ratio (S/co; IQR 4·8-5·9) in recipients of homologous BNT162b2, 4·9 S/co (4·3-5·6) in recipients of homologous ChAdOx1 nCov-19, and 5·6 S/co (5·1-6·1) in recipients of ChAdOx1 nCov-19- BNT162b2. Geometric mean of 50% inhibitory dose against alpha and beta variants were highest in recipients of ChAdOx1 nCov-19-BNT162b2 (956·6, 95% CI 835·6-1095, against alpha and 417·1, 349·3-498·2, against beta) compared with those in recipients of homologous ChAdOx1 nCov-19 (212·5, 131·2-344·4, against alpha and 48·5, 28·4-82·8, against beta; both p<0·0001) or homologous BNT162b2 (369·2, 310·7-438·6, against alpha and 72·4, 60·5-86·5, against beta; both p<0·0001). SARS-CoV-2 S1 T-cell reactivity 3 weeks after boost immunisation was highest in recipients of ChAdOx1 nCov-19-BNT162b2 (median IFN-γ concentration 4762 mIU/mL, IQR 2723-8403) compared with that in recipients of homologous ChAdOx1 nCov-19 (1061 mIU/mL, 599-2274, p<0·0001) and homologous BNT162b2 (2026 mIU/mL, 1459-4621, p=0·0008) vaccination.InterpretationThe heterologous ChAdOx1 nCov-19-BNT162b2 immunisation with 10-12-week interval, recommended in Germany, is well tolerated and improves immunogenicity compared with homologous ChAdOx1 nCov-19 vaccination with 10-12-week interval and BNT162b2 vaccination with 3-week interval. Heterologous prime-boost immunisation strategies for COVID-19 might be generally applicable.FundingForschungsnetzwerk der Universitätsmedizin zu COVID-19, the German Ministry of Education and Research, Zalando SE.

Dataset Information

Impact of timing and combination of different BNT162b2 and ChAdOx1-S COVID-19 basic and booster vaccinations on humoral immunogenicity and reactogenicity in adults.

Publications

Impact of timing and combination of different BNT162b2 and ChAdOx1-S COVID-19 basic and booster vaccinations on humoral immunogenicity and reactogenicity in adults.

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